Inhibition of human neutrophil activity by an RNA aptamer bound to interleukin-8

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• 作者：Ho Jin Sung ; Sooho Choi ; Ji Won Lee ; Chang Youp Ok ; Yoe-Sik Bae ; Yun-Hee Kim ; Weontae Lee ; Kyun Heo ; In-Hoo Kim
• 关键词：Aptamer ; SELEX ; Interleukin-8 (IL-8) ; Nuclear magnetic resonance (NMR) ; Neutrophil
• 刊名：Biomaterials
• 出版年：January, 2014
• 年：2014
• 卷：35
• 期：1
• 页码：578-589
• 全文大小：2947 K

文摘

Interleukin-8 (IL-8) is a proinflammatory CXC chemokine that has been associated with the promotion of neutrophil chemotaxis, degranulation, and the pathogenesis of several neutrophil-infiltrating chronic inflammatory diseases. In the current study, we generated and characterized a 2鈥?fluoro-pyrimidine modified RNA aptamer (8A-35) against human IL-8. The 8A-35 aptamer binds to IL-8 with high specificity and affinity, yielding an estimated K_D of 1.72聽pM. NMR data revealed that the residues of Lys8, Leu10, Val63, Val66, Lys69 and Ala74 of IL-8 interact with aptamer. Moreover, the 8A-35 aptamer has a potent IL-8-neutralizing activity that can modulate multiple biological activities of IL-8 in human neutrophils, including migration, intracellular signaling, and intracellular Ca²⁺ mobilization. Our results suggest that the 8A-35 aptamer has great potential to be a lead structure in the development of effective therapeutic agents against inflammatory diseases.